Background/Purpose: Prolidase is a ubiquitous enzyme found in the cytoplasm.  The enzyme specifically cleaves dipeptides containing C-terminal proline or hydroxyproline, in one of the last steps of collagen metabolism.  Prolidase deficiency is a rare inborn error of metabolism characterized by the secretion of dipeptides in the urine and a variety of clinical manifestations. Only about 50 patients have been reported with the deficiency, of which approximately 10% have systemic lupus erythematosus.  

Methods: A large extended Amish pedigree, having four patients deficient for prolidase, three individuals with heterozygous prolidase activity and eight unaffected individuals, was studied for lupus-associated autoimmunity.  Prolidase genetics and enzyme activity were confirmed.  Antinuclear antibody was measured using indirect immunofluorescence. Antibodies against extractable nuclear antigens were determined by double immunodiffusion, immunoprecipitation, and BioRad 2200 multiplex bead assay.  Serum C1q levels were determined by ELISA.  

Results: Two of the four homozygous prolidase deficient patients had a positive ANA. One had anti-dsDNA antibodies, while another had precipitating anti-Ro60 antibodies.  Three of the four patients had anti-Sm and anti-chromatin by the BioRad 2200 multiplex bead assay. One of the three heterozygous subjects had a positive ANA and immunoprecipitation of a 75,000 MW protein. Serum C1q levels were not changed in the prolidase deficient patients. The unaffected controls had normal prolidase activity and were negative for autoantibodies.

Conclusion: Prolidase deficiency leads to a loss of immune tolerance to lupus-associated autoantigens even without clinical systemic lupus erythematosus.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/prolidase-deficiency-induces-antibodies-to-sm-ro60-and-double-stranded-dna/